NHP PILOT STUDY OF A NOVEL PROTEIN ADJUVANT FOR VACCINES AGAINST HUMAN PATHOGENS

这个子项目是利用资源的许多研究子项目之一 由NIH/NCRR资助的中心拨款提供。次级项目的主要支助 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， NCRR赠款不直接向子项目或子项目工作人员提供资金。 该初步研究的目的是比较实验佐剂rOv-ASP-1与阴性对照（PBS，无佐剂）以及常用佐剂（CpG-C ISS-ODN）的免疫原性和安全性。 2010年4月，六只雄性恒河猴被分配到该项目，并被置于三个实验组之一。 所有动物用50 μ g纯化的rRBD（受体结合结构域）免疫原加对照或测试佐剂皮下免疫三次;组1（n=1）接受PBS（无佐剂），组2（n=2）接受50 μ g rOv-ASP-1，组3（n=2）接受100 μ g rOv-ASP-1，组4（n=1）接受250 μ g CpG-C ISS-ODN。 在每次免疫之前、当天和之后七天收集血液样品以测量抗体和细胞因子应答。 第三次免疫后，抗体滴度显著升高。 根据这些结果，推迟最后两次免疫接种，直至抗体滴度降低。 每月收集血液以监测抗体滴度和细胞因子应答。 最近的结果表明，滴度正在恢复到较低的水平，我们预计在2011年3月对动物进行第四次也是最后一次免疫。 将在免疫前、免疫当天和免疫后第7、30和60天采集血样，以测量抗体和细胞因子应答。 还将在免疫后7天和60天收集淋巴结活检以监测免疫应答。 所有动物将在免疫后第60天后释放至TNPRC。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The purpose of this pilot study is to compare the immunogenicity and safety of the experimental adjuvant rOv-ASP-1 against a negative control (PBS, no adjuvant) as well as a commonly used adjuvant (CpG-C ISS-ODN). Six male rhesus macaques were assigned to this project in April 2010 and placed in one of three experimental groups. All animals were immunized subcutaneously three times with 50ug purified rRBD (receptor binding domain) immunogen plus a control or test adjuvant; Group 1 (n=1) received PBS (no adjuvant), Group 2 (n=2) received 50 ug rOv-ASP-1, Group 3 (n=2) received 100 ug rOv-ASP-1 and Group 4 (n=1) received 250 ug CpG-C ISS-ODN. Blood samples were collected prior to, the day of and seven days after each immunization to measure antibody and cytokine responses. After the third immunization, antibody titers were significantly elevated. Based on these results, the final two immunizations were postponed until the antibody titers diminished. Blood was collected monthly to monitor antibody titers and cytokine responses. Recent results indicate that titers are returning to lower levels and we anticipate immunizing the animals a fourth and last time in March 2011. Blood samples will be collected prior to, the day of and days 7, 30 and 60 post-immunization to measure antibody and cytokine responses. Lymph node biopsies will also be collected 7 and 60 days post-immunization to monitor immune responses. All animals will be released to the TNPRC after the Day 60 post-immunization.